Adverse events were limited and benefits continued when the PCSK9 inhibitor evolocumab was continued for more than 8 years in patients with established atherosclerotic cardiovascular disease, according to results of extension studies following the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trial.
Participants in FOURIER were eligible to receive evolocumab in 2 open-label extension studies, FOURIER-OLE. Pooled data for 6,635 participants were used to look for a primary endpoint of the incidence of adverse events over a median of 5.0 years.
“At 12 weeks in FOURIER-OLE, median LDL-C was 30 mg/dL, and 63.2% of patients achieved LDL-C <40 mg/dL on evolocumab,” the investigators report. “Incidences of serious adverse events, muscle-related events, new-onset diabetes, hemorrhagic stroke, and neurocognitive events with evolocumab long term did not exceed those for placebo-treated patients during the parent study and did not increase over time. During the FOURIER-OLE follow-up period, patients originally randomized in the parent trial to evolocumab versus placebo had a 15% lower risk of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization (hazard ratio, 0.85 [95% CI, 0.75–0.96]; P = 0.008); a 20% lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80 [95% CI, 0.68–0.93]; P = 0.003); and a 23% lower risk of cardiovascular death (hazard ratio, 0.77 [95% CI, 0.60–0.99]; P = 0.04).”